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18-12-2024 | Rhabdomyosarcoma | ORIGINAL ARTICLE

Primary cutaneous rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion: four new cases with distinctive morphology, immunophenotypic, and genetic profile

Authors: Isidro Machado, Eva Wardelmann, Ming Zhao, Jing Song, Yanli Wang, Stephan Alexander Braun, Lluís Catasús, Malena Ferré, Irina Leoveanu, Jula Westhoff, Thomas Rüdiger, Sílvia Bagué

Published in: Virchows Archiv

Abstract

EWSR1/FUS::TFCP2-rearranged rhabdomyosarcoma (RMS) is a rare tumor with an aggressive clinical course, a predilection for craniofacial bones, spindled and/or epithelioid histomorphology, and positive immunohistochemistry (IHC) for epithelial and myogenic markers, along with variable ALK expression. Herein, we present four additional cases of primary cutaneous TFCP2-rearranged RMS. Notably, one tumor (case 1) displayed a varied pathological spectrum, initially presenting as a low-grade spindle cell neoplasm, but progressed into a high-grade spindle/epithelioid tumor. Another case (case 2) exhibited a predominant high-grade epithelioid/rhabdoid morphology. The third case (case 3) demonstrated a biphasic appearance of spindle and epithelioid cell proliferation, presenting with a low-grade morphology, and the last case (case 4) showed a predominant epithelioid morphology. All cases showed myogenic differentiation associated with keratins and ALK immunoreactivity. Interestingly, the two cases with high-grade and epithelioid morphology demonstrated CD30 immunoexpression. RNAseq or FISH revealed EWSR1 or FUS::TFCP2 gene fusion, and two cases with aggressive evolution showed ALK cluster-amplification as well, a finding that has not been previously reported. Two cases displayed aggressive behavior, with case 1 experiencing local recurrences and undergoing transformation into a high-grade epithelioid tumor, whereas case 2 initially presented as an epithelioid high-grade neoplasm, subsequently developing lymph node metastases and shortly thereafter distant metastases. In contrast, patients 3 and 4 are alive with no evidence of disease. The distinctive morphology and immunoprofile of this neoplasm may pose challenges in the differential diagnosis with cutaneous neoplasms showing keratins, ALK, and CD30 immunoreactivity. Nonetheless, ALK and CD30 overexpression may offer avenues for targeted therapy.

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Title: Primary cutaneous rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion: four new cases with distinctive morphology, immunophenotypic, and genetic profile
Authors: Isidro Machado
Eva Wardelmann
Ming Zhao
Jing Song
Yanli Wang
Stephan Alexander Braun
Lluís Catasús
Malena Ferré
Irina Leoveanu
Jula Westhoff
Thomas Rüdiger
Sílvia Bagué
Publication date: 18-12-2024
Publisher: Springer Berlin Heidelberg
Keywords: Rhabdomyosarcoma
Fluorescence in Situ Hybridization
Metastasis
Published in: Virchows Archiv
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-024-04007-z

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Primary cutaneous rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion: four new cases with distinctive morphology, immunophenotypic, and genetic profile

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